Infective complications in patients with secondary haemophagocytic lymphohistiocytosis: a case series from a large central london teaching hospital

Background/Aims Haemophagocytic lymphohistiocytosis (HLH) is a rare systemic inflammatory condition that is characterised by excessive macrophage activation in response to a wide range of triggers, including infections, rheumatological and haematological conditions. HLH is associated with high morbidity and mortality, and treatment requires significant immunosuppression. University College London Hospitals (UCLH) operates an HLH service; we were keen to understand the burden of infective complications in our cohort of patients and establish specific guidelines. Methods A retrospective descriptive analysis was performed of all adults with secondary HLH over a two-year time-frame (1stApril 2019 to 1st April 2021) at UCLH. UCLH has a designated HLH multi-disciplinary team (MDT) supported by rheumatology, infectious diseases, tropical medicine, virology, haematology and critical care. This work was registered as a service evaluation project by the Medical Specialities Division. Data was collated from electronic health records into REDCap, and processed in R version 1.4.1103 and Microsoft Excel by two independent authors. Results 40 patients were identified, with a median age of 37. 14 patients had an identified haematological trigger (35%), 12 an infectious one (30%) and 5 a rheumatological (12.5%). 24 patients (60%) were admitted to intensive care and 13 died during admission (32.5%). 35 patients (87.5%) received steroids at some time during their admission, with 24 (60%) receiving a long course. Four patients (10%) had prolonged neutropaenia during admission. Twenty-four patients (60%) developed an infection during their admission; with 33 bacterial, 7 viral and 12 fungal infections (5 proven, 2 probable and 5 possible) identified. Sixteen patients had >1 infection. Those who did not have a diagnosed infection during their admission were more likely to survive than those who did (93% vs 44%, p = 0.047). The mortality rate of those with fungal infections was 89%, compared to 43% for bacterial and viral infections. Of the 24 patients who received a long course of steroids, 14 (58%) did not receive anti-fungal prophylaxis during their admission and three of these patients were diagnosed with fungal infections during their admission. Of the 4 patients with prolonged neutropenia, 1 (25%) did not receive antifungal prophylaxis and did suffer from a confirmed fungal infection. One patient with confirmed PCP had not previously been taking PCP prophylaxis. Of the seven patients with viral infections, 2 had HSV-1 infections and neither had received anti-viral prophylaxis before their infection start date. Conclusion We demonstrate that a high proportion of patients with HLH develop infective complications, which is associated with increased mortality. Prior to this analysis, the use of antimicrobial prophylaxis was variable. We have since written a specific guideline for the routine use of antimicrobial prophylaxis for patients with HLH, with a view to auditing future care against this guideline. Disclosure P. Saha: None. N. McCann: None. M. Brown: None. N. Stone: None. E. Sanchez: None. B. Carpenter: None. A. Laurence: None. M. Hutchinson: None. A. Jones: None. S.H. Gohil: None. J. Manson: None.